Inhaled vs IV Opioid Dosing for the Initial Treatment of Severe Acute Pain in the Emergency Department

• inhaled titration of morphine chlorhydrate (Drug), also known as IV placebo: Patient in arm A will receive 1 to 3 titration
• IV placebo (Drug), also known as inhaled titration of morphine chlorhydrate: Patient in arm A will receive 1 to 6 injection
• Inhaled placebo (Device), also known as IV titration of morphine chlorhydrate: Patient in arm B will receive 1 to 3 titration
• IV titration of morphine chlorhydrate (Drug), also known as Inhaled placebo: Patient in arm BA will receive 1 to 6 injection

Primary outcomes

• Rate of relief obtained or "success rate" at 1 hour from the start of drug administration, and not at the end of titration, such as EVA1 ≤ 30/100 (or EN1 ≤ 3/10). [1 hour after the initiation of the titration]: Rate of relief obtained or "success rate" at 1 hour from the start of drug administration, and not at the end of titration, such as EVA1 ≤ 30/100 (or EN1 ≤ 3/10).

Secondary outcomes

• Evaluate antalgic efficacy criteria [From the beginning of the titration until the end of the titration- assessed within one day]: Quantity of morphine administered from the beginning of the titration until the end of the titration
• Evaluate antalgic efficacy criteria [From the beginning of the titration until the end of the titration- assessed up to one day]: Delay between first administration of Morphine and EVA ≤ 30 or EN ≤ 3 obtained
• Evaluate antalgic efficacy criteria [From the beginning of the titration until the end of the titration- assessed up to one day]: Delay between first administration of Morphine and EVA ≤ 30 or EN ≤ 3 obtained for patient treated only with morphine IV
• Evaluate antalgic efficacy criteria [From the beginning of the titration until the end of the titration- assessed up to one day]: Number of patients with EVA ≤ 30 or EN ≤ 3 at the end of titration
• Evaluate antalgic efficacy criteria [30 minutes after the initiation of the titration]: Number of patients with EVA ≤ 30 or EN ≤ 3 at 30 minutes
• Evaluate antalgic efficacy criteria [From the beginning of the titration until the end of the titration- assessed up to one day]: Number of patients treated only by exclusive inhalation titration with EVA ≤ 30 or EN ≤ 3
• Evaluate antalgic efficacy criteria [From the beginning of the titration until the end of the titration- assessed up to one day]: Quantity of of co-analgesia administered from the beginning of the titration
• Evaluate antalgic efficacy criteria [1hour after the initiation of the titration]: Number of patients with EVA ≤ 30 or EN ≤ 3 after 60 minutes
• Evaluate antalgic efficacy criteria [2hours after the initiation of the titration]: Number of patients with EVA ≤ 30 or EN ≤ 3 after 120 minutes
• Assess the feasibility of an aerosol titration (compliance to the protocol) [From the beginning of the titration until the end of the aerosol titration- within one hour after the start of the titration]: Number of deviations from protocol
• Safety-Proportion of Sleepy patients (Ramsay score = 3) (adverse events) [Until 3hours after the end of the titration]: Proportion of Sleepy patients (Ramsay score = 3)
• Safety- incidence of minor side effects in each arm of which neurovegetative usually known and related to opiates (nausea, vomiting, urine retention, ...) [Until 3hours after the end of the titration]: incidence of minor side effects in each arm of which neurovegetative usually known and related to opiates (nausea, vomiting, urine retention, ...)
• Safety- Proportion of serious adverse events in each arm [Until 3hours after the end of the titration]: Proportion of serious adverse events in each arm

Sex: All, ages: 18 Years to 75 Years

Inclusion Criteria:

* Age ≥ 18 and <75 years old;
* EVA ≥ 70/100 or EN ≥ 7/10;
* Patient who received clear information from the investigator and read and signed the consent form;
* Patient affiliated with, or beneficiary of a social security category;
* For women:

O of childbearing age: effective contraception (oral contraception, intrauterine device or use of condoms) O menopausal status (amenorrhoea less than 12 months before the inclusion visit) O objectivized sterility (diagnosis or surgically)

Exclusion Criteria:

* Chronic pain (> 3 months)
* Taking opioids longer than 10 days (including "weak" opioids tramadol and / or codeine);
* Taking Rifampicin;
* Impaired ability to discern, cognitive impairment;
* Morphine-related contraindications:

O Obstructive chronic obstructive or restrictive respiratory failure known or suspected compensated or not, O Hypersensitivity to the active substance or to any of the excipients, O Severe hepatocellular insufficiency (known or suspected), O Chronic renal failure known or suspected, O Uncontrolled epilepsy, O Cranial trauma (intracranial hypertension), O Associations with buprenorphine, nalbuphine, pentazocine and naltrexone

* Active drug history or practice (s);
* Evidence of reduced fracture or dislocation in emergency rooms;
* Suspected occlusive syndrome
* SaO2 <95%;
* FR <12 / min;
* Glasgow <15 or other alertness disorders;
* HR heart rate <50 bpm and / or Auriculo-Ventricular block (PR XML File Identifier: zR6XOYKSEQ9GjQHghP8c465EwF0= Page 15/30 interval> 200 ms);
* Arterial hypotension with systolic blood pressure TA syst <100 mm Hg;
* Pregnant or nursing
* Persons deprived of their liberty by an administrative or judicial decision, a person placed under the safeguard of justice, guardianship;
* Patients with poor comprehension of spoken or written French;
* Patients participating in another interventional clinical study;
* Contra-indication related to the use of saline solution
* Contra-indications related to the use of aerosol:

O Necessity to access the face O Allergy known to plastic

• Results publication: Lvovschi VE, Joly J, Lemaire N, Maignan M, Canavaggio P, Leroi AM, Tavolacci MP, Joly LM. Nebulized versus intravenous morphine titration for the initial treatment of severe acute pain in the emergency department: study protocol for a multicenter, prospective randomized and controlled trial, CLIN-AEROMORPH. Trials. 2019 Apr 11;20(1):209. doi: 10.1186/s13063-019-3326-3. PMID 30975187